Progress in neurobiologyJul 20, 2010

Roles of Gut- and Brain-Made GLP-1, GLP-2, and Oxyntomodulin Peptides in the Brain

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 27, 2026

Abstract

Preproglucagon derived peptides are linked to two classes of glucose lowering agents for type 2 diabetes, DPP-IV inhibitors and GLP-1 receptor agonists.

GLP-1 receptor agonists may play a role in the central nervous system as neurotransmitters.
There is limited understanding of how central GLP-1 receptors are influenced by GLP-1 receptor agonists administered from outside the brain.
GLP-1 is recognized as an anorectic neurotransmitter, but further investigation is needed to clarify its neuronal targets and physiological roles.
Recent evidence suggests that GLP-1 may have neuroprotective properties that could impact various neurodegenerative conditions.

Simplified

The scientific understanding of preproglucagon derived peptides has provided people with type 2 diabetes with two novel classes of glucose lowering agents, the dipeptidyl peptidase IV (DPP-IV) inhibitors and GLP-1 receptor agonists. For the scientists, the novel GLP-1 agonists, and DPP-IV inhibitors have evolved as useful tools to understand the role of the preproglucagon derived peptides in normal physiology and disease. However, the overwhelming interest attracted by GLP-1 analogues as potent incretins has somewhat clouded the efforts to understand the importance of preproglucagon derived peptides in other physiological contexts. In particular, our neurobiological understanding of the preproglucagon expressing neuronal pathways in the central nervous system as well as the degree to which central GLP-1 receptors are targeted by peripherally administered GLP-1 receptor agonists is still fairly limited. The role of GLP-1 as an anorectic neurotransmitter is well recognized, but clarification of the neuronal targets and physiological basis of this response is further warranted, as is the mapping of GLP-1 sensitive neurons involved in a variety of neuroendocrine and behavioral responses. Further recent evidence points to GLP-1 as a central neuropeptide with neuroprotective capabilities potentially mitigating a wide array of neurodegenerative conditions. It is the aim of the present review to summarize our current understanding of preproglucagon derived peptides as neurotransmitters in the central nervous system.

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Roles of Gut- and Brain-Made GLP-1, GLP-2, and Oxyntomodulin Peptides in the Brain

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